1. Field of the Invention
The present invention is directed to Lactobacillus mali, particularly to Lactobacillus mali APS1 that is for preventing or treating metabolic syndrome such as obesity, diabetes and complications thereof.
2. Description of Related Art
Due to the changes of habits and customs, obesity becomes the latest epidemic disease (Bleich et al., 2008) and its morbidity is still increasing in the world. According to the estimation from World Health Organization, the obese population will reach 6 million in 2025 (Serino et al., 2009). Obesity is defined as the expanded adipose cells due to excessive accumulation of fat content in body. The weight gain accompanied by abnormal metabolism is mainly contributed by excessive intake of diets which are rich in nutrients. The obese population is a high-risk group of potential complex metabolic syndrome which involves the complex pathological conditions comprising insulin resistance (IR), glucose tolerance change, fatty liver and dyslipidemia, and is associated with various metabolic diseases such as type 2 diabetes and cardiovascular diseases.
According to the statistical results from Ministry of Health and Welfare, Taiwan, diabetes is the fourth cause of top-ten leading causes of death in Taiwan, wherein 95% of diabetes patients belong to non-hereditary type 2 diabetes (Ministry of Health and Welfare, Executive Yuan, 2012). In addition to the high blood glucose level contributed by impaired ability of glucose metabolism, the complications such as retinopathy, nephropathy, and neuropathy and cardiovascular diseases may be developed in a patient suffering from serious diabetes, resulting in greatly increased mortality. However, there is no effective medical treatment for type 2 diabetes. The suggested treatment of type 2 diabetes is still surrounding the control diet and increased amount of exercises.
There are more and more evidences supporting that inflammation plays a critical role in the development of metabolic diseases (Hotamisligil, 2006). Under the condition of long-term nutrition overload, in particular the chronic and low degree inflammation induced by visceral fat, infiltration of macrophages produces a great amount of pro-inflammatory cytokines and chemokines, such as leptin, tumor necrosis factor-α (TNF-α), macrophage chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). The function of adipose tissue is changed by these products and the intrinsic adipose cells in adipose tissue of obesity subjects, and the storage of triglyceride and the cycles of free fatty acid are also impaired. Therefore, the pathological disorders in the obesity subject as well as insulin resistance are induced (Fantuzzi, 2005; Sesti, 2006).
Recently, many studies found that intestinal microbiota is significantly relevant to obesity (Backhed et al., 2007). The composition of intestinal microorganisms in healthy subject is very different from that in obese/type 2 diabetes patient, indicating that such composition is an important factor resulting in these metabolic diseases (Cani et al., 2009; Caesar et al., 2010; Musso et al., 2010; Delzenne and Cani, 2011; Frazier et al., 2011; Greiner and Bäckhed, 2011; Cani et al., 2012; Tremaroli and Bäckhed, 2012).
The nutrition source of intestinal microorganisms is mainly from the host's diet, and their interaction can generate energy and stimulate immune system and endocrine (Delzenne and Cani, 2011; Tremaroli and Bäckhed, 2012). In the intestinal microorganisms, the ratio of Gram positive/negative bacteria is closely relevant to the energy metabolism in the host, the endotoxin level in blood and the regulation of inflammation response. Although the mechanism is unclear yet, the interaction of intestinal microorganisms, host gene expression and lifestyle may generate the metabolic symptoms such as obesity and diabetes (Cani et al., 2007 (1); Lye et al., 2009).
Accordingly, probiotics applications gradually emerge in the studies of improving metabolic symptoms. Common probiotics belong to Gram positive bacteria, such as Lactobacillus sp. and Bifidobacterium sp., which enhance the host health by, for example, inhibiting the growth of pathogen, facilitating the equilibrium of intestinal microbiota, decreasing lactose intolerance and food allergy (McFarland et al., 2000; Anderson et al., 2001; Salminen et al., 2001).
In view of the studies, in Matsuzaki et al. (1997), the insulin-resistance KK-Ay mice were fed with live and dead Lactobacillus casei, and found that the blood glucose level and the weights were significantly decreased in eight- to ten-week-old mice. As to the experiment of inducing diabetes symptoms in mice by high-fat diet (HFD), in Cani et al. (2007 (2)), HFD mice fed with the mixed Bifidobacterium sp. could improve glucose tolerance and decrease the weight of visceral adipose tissue, in comparing to the control group. In Yadav et al. (2007), mice having hyperglycemia induced by high glucose diet were fed with an India traditional fermentation product containing live Lactobacillus acidophilus and Lactobacillus casei, and found that mice with this fermented product could significantly reduce the glucose tolerance and the levels of the glucose concentration, total cholesterol, triglyceride, low-density lipoprotein, very low-density lipoprotein and volatile fatty acid in blood, in comparing to the control group. It is thus suggested that the fermentation product containing live Lactobacillus acidophilus and Lactobacillus casei can reduce the progression of type 2 diabetes induced by obesity.
It can be seen that the ability of probiotics in regulating immunity, decreasing cholesterol level in blood, preventing hypertension, improving eating disorders and alleviating diabetes has been applied in prevention and clinical treatment of metabolic diseases (Lye et al., 2009).